Table 2 List of clinical trials testing the efficacy of drugs active in autophagy modulation in cancer and pulmonary/liver fibrosis
From: Nanomedicine for autophagy modulation in cancer therapy: a clinical perspective
Therapeutic name | Mechanism of action | Delivery system | Target(s) | Cancer type | Phase | NCT ID |
|---|---|---|---|---|---|---|
Chloroquine (CQ) | Inhibits autophagosome fusion with lysosome and autophagosome degradation | Hybrid dendritic-linear-dendritic block copolymers | Lysosomotropic agent; lysosomal pH | Non-small-cell lung cancer | I/II | NCT00969306 |
Hydroxychloroquine (HCQ) | Inhibits lysosomal acidification and prevent the degradation of autophagosomes | Liposomes decorated with a pH-sensitive TH-RGD targeting peptide | Lysosomotropic agent; lysosomal pH | Prostate cancer | II | NCT00726596 |
Breast cancer | II | NCT04841148 | ||||
Solid tumors undergoing radiation therapy for bone metastases | I | NCT01417403 | ||||
HCQ + Tamoxifen (TAM) | Antiestrogenic activity | Lysosomotropic agent; lysosomal pH; estrogen receptor | Breast | I/II | NCT01023477 | |
Temozolomide | Induces G2 cell cycle arrest | ABI-009 nanocomplex | Genotoxic stress | Refractory solid tumors | I | NCT02975882 |
Dasatinib | ATP-competitive small-molecule inhibitor | BCR/ABL and Src family tyrosine kinases | Glioblastoma | II | NCT00423735 | |
Bortezomib | Increases the early formation of autophagosomes and LC3-II | Liposomes | Proteasome inhibitor | Multiple myeloma | I/II | NTC00568880 |
Temsirolimus | Promotes apoptosis and causes the downregulation of mTOR phospho-S6 | mTOR | Metastatic solid tumors | I | NTC00909831 | |
Everolimus | Angiogenesis inhibitor; G1 cell-cycle arrest | mTOR | Mantle cell lymphoma | II | NCT00436618 | |
Nab-Paclitaxel (AB-007) | Promotes microtubule assembly and stabilization | Albumin | Cytoskeleton | Breast cancer | Approved | NCT02555696 |
Rapamycin | Cell viability reduction and decreased mTOR downstream signaling | ABI-007 | mTOR | Advanced solid tumors | Ib | NCT00408655, NCT01369433, NCT01014351 |
Nab-rapamycin (ABI-009) | Cell viability reduction and decreased mTOR downstream signaling | Nanoparticle’s albumin–bound | mTOR targets S6K and 4EBP1 | Unresectable advanced non-hematologic malignancies | I | NCT00635284, NCT02646319, NCT03817515 |
Carboplatin | Cross-linking/alkylating agent | Nab-paclitaxel (ABI-007) | DNA | Advanced or metastatic non–small cell lung cancer | III | NCT02799862 |
Gemcitabine | Cross-linking/alkylating agent | (ABI-007) | DNA | Metastatic pancreatic adenocarcinoma | II | NCT03529175 |
ABI-009 complex | NMIBC | I/II | NTC02009332 | |||
3-MA + Trastuzumab (Tmab) | Prevents autophagosome formation | Gold nanoparticle | PI3K inhibition | HER-2 + breast cancer | III | NCT03529110 |
HCQ + FOLFOX/bevacizumab | Binds and inactivates serum VEGF | ABI-009 complex | Angiogenesis inhibitor | Colorectal cancer | I/II | NCT01206530 |
HCQ + pazopanib | Antineoplastic agent | ABI-009 complex | VEGF receptor | Sarcoma | I/II | NCT03660930 |
HCQ + nivolumab | PD-1 blocking antibody | ABI-009 complex | PD-1 | Sarcoma, colorectal cancer | I/II | NCT03190174 |
MRX34 | Inhibition of tumor associated EMT | Lipid nanoparticle | MiR-34 specific targets | Solid tumors refractory to standard treatment | I | NCT01829971 |
SNAs | Targets the oncoprotein Bcl2Like12 a caspase effector and p53 inhibitor overexpressed in GBM | Gold nanoparticle | Bcl2L12 mRNA | Glioblastoma multiforme (GBM) | I | NTC03020017 |
ND-L02-s0201 | Targets heat shock protein 47 (HSP47) in hepatic stellate cells which have key roles in liver homeostasis as well as uptake and storage of vitamin A | Vitamin-A coupled liposome | Heat shock protein 47 (HSP47) | Pulmonary/liver fibrosis | I/II | NCT03538301 NCT03241264 NCT02227459 NCT01858935 |